Combinatorial Atoh1 and Gfi1 induction enhances hair cell regeneration in the adult cochlea.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 12 2020
08 12 2020
Historique:
received:
18
08
2020
accepted:
19
11
2020
entrez:
9
12
2020
pubmed:
10
12
2020
medline:
25
3
2021
Statut:
epublish
Résumé
Mature mammalian cochlear hair cells (HCs) do not spontaneously regenerate once lost, leading to life-long hearing deficits. Attempts to induce HC regeneration in adult mammals have used over-expression of the HC-specific transcription factor Atoh1, but to date this approach has yielded low and variable efficiency of HC production. Gfi1 is a transcription factor important for HC development and survival. We evaluated the combinatorial effects of Atoh1 and Gfi1 over-expression on HC regeneration using gene transfer methods in neonatal cochlear explants, and in vivo in adult mice. Adenoviral over-expression of Atoh1 and Gfi1 in cultured neonatal cochlear explants resulted in numerous ectopic HC-like cells (HCLCs), with significantly more cells in Atoh1 + Gfi1 cultures than Atoh1 alone. In vitro, ectopic HCLCs emerged in regions medial to inner HCs as well as in the stria vascularis. In vivo experiments were performed in mature Pou4f3
Identifiants
pubmed: 33293609
doi: 10.1038/s41598-020-78167-8
pii: 10.1038/s41598-020-78167-8
pmc: PMC7722738
doi:
Substances chimiques
Atoh1 protein, mouse
0
Basic Helix-Loop-Helix Transcription Factors
0
DNA-Binding Proteins
0
Gfi1 protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
21397Subventions
Organisme : NIDCD NIH HHS
ID : R01-DC014832
Pays : United States
Organisme : NIDCD NIH HHS
ID : R21-DC016171
Pays : United States
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